Nutrient sensing modulates malaria parasite virulence

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence

Evolution of the TOR Pathway

The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provide a practical framework on which experimental evidence can be compared between species. Here we performed phylogenetic analyses on the components of the TOR pathway and determined their point of invention. We find that the two TOR complexes and a large part of the TOR pathway originated before the Last Eukaryotic Common Ancestor and form a core to which new inputs have been added during animal evolution. In addition, we provide insight into how duplications and sub-functionalization of the S6K, RSK, SGK and PKB kinases shaped the complexity of the TOR pathway. In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes

Modeling the effect of temperature and wetness on <I>Guignardia </I>pseudothecium maturation and ascospore release in citrus orchards

Please help populate SUNScholar with the full text of SU research output. Also - should you need this item urgently, please send us the details and we will try to get hold of the full text as quick possible. E-mail to [email protected]. Thank you.Journal Articles (subsidised)AgriwetenskappePlantpatologi

Die sheet hydroforming of a complex-shaped AA2024-W aircraft skin panel — from concept to final component

CITATION: Serfontein, J. L., et al. 2021. Die sheet hydroforming of a complex-shaped AA2024-W aircraft skin panel — from concept to final component. South African Journal of Industrial Engineering, 32(4):13-27, doi:10.7166/32-4-2502.The original publication is available at http://sajie.journals.ac.zaENGLISH ABSTRACT: In terms of project risk management, ‘systemic risk’ is identified as risks which are artefacts of the environment which a project is executed in, and are related to (i) the project team’s actions, (ii) how project controls are managed and interact, and (iii) how the project is planned and executed. This paper proposes a methodology to estimate the cost impact of systemic risk on a portfolio of projects by using risk quantification and Monte Carlo simulation, in the absence of a validated parametric risk model, to estimate the systemic risks in an entire portfolio of projects. The case study simulation results indicate a significant effect of systemic risks on the project portfolio risk profile, where systemic risks increased the P80 value of the contingency requirement by +85.6%. The successful management of systemic risk would contribute to project success by limiting unnecessary waste.AFRIKAANSE OPSOMMING: In die vroeë stadiums vereis produkontwerp ’n meer kwantitatiewe proses om seker te maak dat die simulasiestudie se uitkoms aan die verwagtinge voldoen. Die doel van hierdie studie was om vas te stel of ’n simulasiepakket vir vervaardigingsimulasie die stempelplaat-hidrovorming van ʼn aluminiumligering vliegtuigpaneel met ʼn komplekse vorm doeltreffend kon evalueer en staaf. Die ru-stuk- en persgereedskap konsepte is digitaal gekonseptualiseer, geëvalueer, en gestaaf met behulp van die konseptualiseringsiklus van die vormingsproses. Omdat dit nie nodig was om verskeie ru-stuk- en persgereedskap konsepte fisies te toets nie, is daar beduidend bespaar deur die gebruik van ’n hulpbron- doeltreffende ontwikkelingsproses. Selfs sonder die modellering van die hiperelastiese rubberelemente kon ʼn suksesvolle hidrovormingsimulasie- uitslag behaal word. Die studie het egter getoon dat ʼn rubber-op-metaal- wrywingskoëffisiënt toepaslik geïnkorporeer moet word. Die studie dui op die gebrek aan standaard metrologiemetodes vir die akkurate evaluering van ʼn simulasie-uitslag in kommersiële simulasiepakkette. Simulasie- metrologie is ʼn nuwe belangstellingsgebied wat verder ontwikkel moet word. Die navorsing dra by tot die verbetering van die simulasieproses van plaatmetaalvorming, en spesifiek die simulasie van die stempelplaat- hidrovormingsproses. Die studie is van nut vir die ruimtevaart- en motorbedryf en bevorder die aanvaarding van digitale vervaardigings- prosesse.Publisher's versio

Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the cape ground squirrel (Xerus inauris)

The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris) undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6±9.2 µg/kg, ketamine 13.6±1.9 mg/kg and buprenorphine 0.5±0.06 µg/kg. Induction time was 3.1 ± 1.4 min. This produced surgical anaesthesia for 21± 4.2 min. Atipamezole 232±92 µg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 ± 2.2 min